Effects of isoprenoid compounds on human solid cancer cells

我们检测了类异戊二烯化合物如香叶基香叶醇和维生素1 β 2或来自人体组织的各种实体癌细胞系的作用。香叶基香叶醇在本研究中检测的每种癌细胞中诱导凋亡。1C 50值的范围为30 - 90 μ M。另一方面，在分子中还含有香叶基香叶基的维生素K2仅在两种细胞系如胰腺癌MIA-PaCa 2细胞和卵巢癌TYK-nu细胞中诱导凋亡。当这些细胞用维生素K2处理时，它们在孵育后4天收缩并形成小的凋亡小体。放线菌酮和放线菌素D抑制维生素K2诱导的细胞凋亡，表明蛋白质合成是维生素K2诱导细胞凋亡所必需的。放线菌酮对香叶基香叶醇诱导的细胞凋亡无明显抑制作用。在白血病U937细胞中，JNK和半胱天冬酶3被激活的治疗与香叶基香叶醇，而这些酶没有被激活的维生素K2。这些结果表明，香叶基香叶醇和维生素K2可能通过不同的机制诱导细胞凋亡。

We examined the effects of isoprenoid compounds such as geranylgeraniol and vitamin 1(2 or various solid cancer cell lines derived from human tissues. Geranylgeraniol induced apoptosis in every cancer cells examined in the present study. The 1C50 values range from 3O-9O muM.On the other hand, vitamin K2 that also contains a geranylgeranyl group in the molecule induced apoptosis only in two cell lines such as pancreatic cancer MIA-PaCa 2 cells and ovary cancer TYK-nu cells. When these cells were treated with vitamin K2, they shrank and small apoptotic bodies were formed 4 days after the incubation. Cycloheximide and actinomycin D inhibited the induction of apoptosis by vitamin K2, suggesting protein synthesis is necessary for apoptosis by vitamin K2. By contrast, the apoptosis induced by geranylgeraniol was not inbhibited by cycloheximide. In leukemia U937 cells, both JNK and caspase 3 were activated by the treatment with geranylgeraniol, while these enzymes were not activated by vitamin K2. These results suggest that geranylgeraniol and vitamin K2 might induce apoptosis by different mechanisms.